Amine salts of chlorophenols



United States Patent 2,806,063 AMINE SALTS F CHLOROPHENOLS Raymond H. Rigterink, Midland, Mich., assignorto The Dow Chemical Company, Midland, Mich., .a corporation of Delaware No Drawing. Application April .23, 1956, Serial ,No. 579,775

6 Claims. (Cl. 1260-95615) This invention is concerned with amine salts of chlorophenols having the structure 7 pounds are useful as toxicants rn microbicidal compositions, such as in bactericidal and fungicidal preparations. They have the advantage of increased water solubility and decreased vapor pressure over certain known antimicrobial compositions. V

The new amine salts of chlorophenols maybe prepared by combining a chlorophenol :having the structure with an a-aminocresol compound having the formula The reaction takes place readily in the temperature range of 20 to 80 C. with the formation of the desired salt. An inert solvent such as ethanol or isopropanol provides a convenient reaction medium. Good results are obtained when substantially equimolar amounts of the chlorophenol and cr-amiIlOCI'CSOI compound are employed.

-In carrying out the reaction, the chlorophenol and a-aminocresol are dissolved in the solvent and the resulting mixture heated for a periodof from a few minutes to about one hour. After completion of the reaction, the reactionmixture is heated to distill the water of reaction and solvent and to recover as residue the salt product. The latter may be purified by conventional methods such as recrystallization or distillation under reduced pressure. A particular group of the new amine salts having the structure Patented Sept. 10,

ice

may be prepared by causing a chlorqphenol, a suitable amine and formaldehyde to interact. Suitable'amines include dimethylamine, diethylamine, piperidine, morpholine, cyclohexylamine and primary aliphatic amines such as methylamine, ethylamine, butylamine, octylamine and dodecylamine. The reaction is usually carried out in an inert polar solvent such as ethanol and takes place readily in the temperature range of from 20 to C. with the formation of the desired compound. Good results are obtained when substantially two molecularproportions of the phenolic compound are employed with one molecular proportion of formaldehyde and one molecular proper.

tion of the amine.

In carrying out the latter reaction, the chlorophenol, the formaldehyde .and the amine .are.dissolved in the reaction solvent. The mixture is heated for aperiod ofirom about one-half to two hours at the boiling temperature under reflux. At the end .of this period, the mixture is distilled to remove the solvent and water. The salt product residue may be purified, if desired, by recrystallization.

The following examples illustrate the invention, but

are

not to be construed as limiting.

Example 1 OH OH ,01- CHzNQCHeh vor C1 {C1 I 1 c1 44.6 grams (0.55 mole) of 36-38 percent aqueous formaldehyde was added portionwise :to a stirred mixture of 98.8 grams 0.5 mole) of 2,4,5-trichlorophenol and 270 grams (1.5 moles) of 25 percent aqueous dimethylamine while the temperature of the mixture was maintained at 25 to 30 C. The resulting solution was stirred and heated for two hours at reflux temperature and then distilled to remove most of the dimethylamine and water. After completion of the distillation, the mixture was cooled and the residue dissolved in toluene and washed repeatedly with water. The toluene solution was heated first at atmospheric pressure and then at reduced pres sure to distill the toluene solvent and to obtain as residue a light brown crystalline a-dimethylamino-ii,4,6-trichloroo-cresol salt of 2,4,5-trichlorophenol. This product, after recrystallization first from petroleum ether (B. P. 60 70 C.) and then from toluene, melted at l20l22' (1., and had a'nitrogen content of 3.17 percent. The theoretical value is 3.11 percent.

Example 2 C Hr-N (C Hz) a CHa-Jl-CH: 01

49.4 grains {0.25 mole) of 2,4;5-trichlorophenol and 51.8 grams (0.25 mole) of 4-ter tiary butyl-ot-dirnethyl amino-o-cresol were dissolved in 100 milliliters of percent ethanol and heated at the boiling'point under reflux for one hour. The mixture was stirred during the heating. After completion of the heating, the clearre'action solution was fractionally distilled to obtain'a yellow viscous oil 'boiling from to C. at 0.5 millimeters pressure. On standing, the oil changed to a waxy solid .4-tertiary-butyl--dimethylamino-o-cresol" salt of petroleum ether (B. P. -86-100 2,4,5-trichlorophenol as a product melting from 80 to 93 C.

Example 3 81.5 grams (0.5

water and to obtain as an oily residue a 4,6-dichloro-adimethylamino-o-cresol salt of 2,4dichlorophenol. This product crystallized on standing to a solid melting from 755' to 78 C.

Example 4 98.8 grams (0.5 mole) of 2,4,5-trichlorophenol, 21.8 grams (0.25 mole) of morpholine, 20.3 grams (0.25 mole) of 36-38 percent formaldehyde and 200 milliliters of 95 percent ethanol were heated and stirred at the boiling point under reflux for one hour. The pressure on the system was reduced and the heating con-' tinued to distill alcohol and water and to obtain as residue a dark red, viscous oil. The oil crystallized on standing to a 3,4,6-trichloro-a-morpholino-o-cresol salt of 2,4,5-trichlorophenol as a product melting from 59 to 62 C.

Example 5 In a synthesis carried out in a manner similar to that described in Example 4, 98.8 grams (0.5 mole) of 2,4,5-trichlorophenol, 20.4 grams (0.25 mole) of 36-38 percent aqueous formaldehyde, 18.3 grams (0.25 mole) of diethylamine and 200 milliliters of 95 percent ethanol were caused to interact and to obtain a dark reddish brown oily a-diethylamino-3,4,6-trichloro-o-cresol salt of 2,4,5-trichlorophenol. This product had a nitrogen content of 2.50 percent, the theoretical value being 2.92 percent.

Example 6 19.8 grams (0.1 mole) of 2,4,5-trichlorophenol and 23.0 grams (0.1 mole) of 4,6-dichloro-a-dimethylaminoo-cresol were added to 100 milliliters of 95 percent ethanol and dissolved therein by warming on a steam bath. The clear solution so formed was cooled in ice-water whereupon crystals of unreacted 4,6-dichloro-a-dimethylamino-o-cresol precipitated. These crystals were removed by filtration. The filtrate was diluted with water whereupon an oil precipitated. The heterogeneous liquid mixture was heated at reduced pressure to distill the alcohol and water and to recover as residue a dark brown oily 4,6-dichloro-ot-dimethylamino-o-cresol salt of 2,4,5-trichlorophenol. This crude product was purified by repeated treatment comprising dissolving the oil in warm petroleum ether (B. P. 86-100 C.), cooling the resulting solution to reprecipitate the oily product and decanting the solvent layer. The resulting residue was a brown viscous liquid having a nitrogen content of 3.12 percent. The theoretical value is 3.35 percent. Infrared analysis indicated the product to be a salt of 2,4,5- trichlorophenol.

Example 7 112 grams (0.363 mole) of a-cyclohexylamino-3,4,6- tn'chloro-o-cresol was dissolved in 300 milliliters of ethanol by warming on the steam bath and 71.6 grams (0.363 mole) of 2,4,5-trichlorophenol was added thereto. The resulting solution was distilled to remove alcohol solvent and to obtain as residue a 3,4,6-triChl01O-ozcyclohexylamino-o-cresol salt of 2,4,5-trichl0rophenol. This product was purified by repeated washing with C.) to obtain a white crystalline product melting at 143 l44.5 C. The latter had a chlorine content of 41.62 percent and a nitrogen amino-o-cresol i of 2,4-dichlorophenol.

4 and heated under reflux with stirring cold ethanol, dried at 4 content of 2.80 percent. The theoretical values are 42.1 percent and 2.77 percent, respectively.

Example 8 Example 9 81.5 grams (0.5 mole) of 2,4-dichlorophenol and 116.57 grams (0.5 mole) of 4,5-dimethyl-m-cyclohexylare dissolved in 200 milliliters of 95 percent ethanol and heated at the boiling point under reflux for one hour. The mixture is stirred during the heating. At the end of this period, the pressure on the system is reduced and the water and solvent distilled to obtain as residue a 4,S-dimethyl-a-cyclohexylamino-o-cresol salt The latter is washed repeatedly with petroleum ether to obtain a purified product having a molecular weight of 279.5.

Example 10 197.5 grams (1.0 mole) of 2,4,5-trichlorophenol, 75 grams (0.5 mole) of 30 percent aqueous ethylamine, and 40.7 grams (0.5 mole) of 37-38 percent aqueous formaldehyde in 100 milliliters of ethanol were mixed for two hours. The mixture was then cooled whereupon it became a semisolid mass. The latter was filtered to obtain a crystalline 3,4,6 trichloro 0c ethylamino o cresol salt of -2,4,5-trichlorophenol. This product was washed with room temperature, and recrystallized from toluene. The recrystallized product melted at 125 l27 C. and had a chlorine content of 47.87 percent. The theoretical value is 47.2 percent.

Example 11 with ice cold petroleum ether and drying at room temperature melted at 85 -87 C.

In preparations carried out in a manner similar to that described in Example 11, other amine salts may be prepared from the respective aminocresols and chlorophenols, as, for example, 3,4,6-trichloro-a-methylamino o-cresol salt of 3,4,6-trichlorophenol; 3,4,6-trichloro-a-octylaminoo-cresol salt of 3,4,6-trichlorophenol and 4,6-dichloroa secondary butylamino o cresol with 2,4- dichlorophenol. I

The a-aminocresol compound having the structure CHrR may be prepared by mixing equimolar proportions of the appropriate phenol, formaldehyde and amine in a solvent such as ethanol, usually with cooling. The mixture is stirred and heated under reflux from one-half to several hours, and then allowed to cool to room temperature. The desired u-amino-cresol may precipitate on aeoaoes cooling whereupon it can be isolated by filtration. If no precipitation of the a-amino-cresol occurs, the mixture may be heated to distill the solvents and obtain the desired product as residue. The latter may be employed in the preparation of the salt without purification.

The products of the present invention may be employed as toxicants in parasiticidal compositions. In a representative operation, a 3,4,6-trichloro-a-rnorpholinoo-cresol salt of 2,4,5-trichlorophen0l was added to a medium inoculated with Salmonella typhosa and incubated at 30 C. for four days. Examination at the end of this period showed complete inhibition of growth of the test organisms when the concentration of the salt in the medium was 0.005 percent.

1 claim:

1. An amine salt of a chlorophenol having the formula (?H OH CHuR wherein R is a member of a group consisting of alkylarnino, dimethylamino, diethylarnino, cyclohexylamino, piperidino and morpholino, X is a member of the group consisting of chlorine and lower alkyl, m is an integer from 1 to 3, inclusive, and n is an integer from 2 to 3, inclusive. 7

2. a Dimethylamino 3,4,6 trichloro-o-cresol salt of 2,4,5-trichlorophenol.

3. 4 tertiary butyl a dimethylamino 0 salt of 2,4,5-trichlorophenol.

4-. 3,4,6 trichloro o: cyclohexylarnino o cresol salt of 2,4,5-trichlorophenol.

5. 3,4,6 trichloro cc ethylamino of 2,4,5-trichlorophenol.

6. 3,4,6 trichloro 0c of 2,4,5-trichlorophenol.

- cresol o cresol salt dodecylamino o cresol salt No references cited. 

1. AN AMINE SALT OF A CHOROPHENOL HAVING THR FORMULA 